Lipid aggregates such as liposomes have been found to be useful as delivery agents to introduce macromolecules, such as DNA, RNA, proteins, and small chemical compounds such as small molecules or pharmaceutically active molecules, to cells and tissues in laboratory and clinical research settings. In particular, lipid aggregates comprising cationic lipid components have been shown to be especially effective for delivering anionic molecules to cells. In part, the effectiveness of cationic lipids, and positively charged complexes formed with cationic lipids, is thought to result from enhanced affinity for cells, many of which bear a net negative charge. Also in part, the net positive charge on lipid aggregates comprising a cationic lipid enables the aggregate to bind polyanions, such as nucleic acids. Lipid aggregates containing DNA and RNA are known to be effective agents for efficient transfection of target cells
Messenger RNA (mRNA)-based gene delivery has generated much interest in recent years. mRNA transfection has several advantages plasmid or vector-based transfection methodologies, including a lack of requirement for nuclear entry, which poses a significant barrier to plasmid DNA (pDNA) delivery, especially in non-dividing cells. mRNA also has a negligible chance of integrating into the host genome. (mRNA) is frequently applied as a gene delivery molecule in the field of cancer immunotherapy and stem cell-based research as an alternative to pDNA. In addition, a rapidly growing interest in using mRNA instead of pDNA for iPS cell reprogramming, genome editing (CRISPR, TALEN) and vaccine development has emerged.
Despite the advantages of mRNA transfection over DNA, there are few commercially available reagents that can efficiently and consistently yield high transfection efficiencies of cargo mRNA over a wide variety of cell types and lineages, such as primary cells, neuronal cells, blood cells, stem cells and difficult to transfect cell lines.
Thus, there exists a need for lipid aggregate formulations that are capable of delivery a variety of cargos to a wide spectrum of cell lineages and difficult to transfect cells.